1.Role of alkaloid compounds in regulating chronic liver diseases
Yihui ZHENG ; Jiahui WANG ; Tiejian ZHAO ; Xuelin DUAN ; Lei WANG ; Yang ZHENG ; Shiquan YANG
Journal of Clinical Hepatology 2025;41(2):375-382
Chronic liver diseases with common causes including viral infections, alcohol abuse, and autoimmune diseases. Alkaloids, as a class of plant-derived compounds, have shown significant potential in regulating chronic liver diseases. Recent studies have shown that alkaloids are able to exert a therapeutic effect on chronic liver diseases through multiple pathways. These compounds have a regulatory effect on key pathological processes such as liver fibrosis, inflammatory response, oxidative stress, and cell apoptosis, and they also regulate the metabolic homeostasis of hepatocytes by modulating multiple signaling pathways, thereby playing a role in regulating chronic liver diseases. This article reviews the role and mechanism of alkaloids in the treatment of chronic liver diseases, in order to provide new ideas and directions for the treatment of chronic liver diseases.
2.Mechanism of Qingre Huayu Jianpi Prescription Inhibiting Development of Colitis-associated Colorectal Cancer in Mice
Yanqiu ZHENG ; Yihui YOU ; Junyu KE ; Jinbin SONG ; Yongqiang WU ; Changhui LIU ; Yanwu LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(8):83-90
ObjectiveTo explore the effect of Qingre Huayu Jianpi prescription (QHJ) on colitis-associated colorectal cancer (CAC) in mice, and its related mechanism. MethodC57BL/6 mice were randomly divided into four groups including the normal, model, QHJ low-dose (QHJ-L, 10 g·kg-1), and QHJ high-dose (QHJ-H, 40 g·kg-1) groups. Azoxymethane (AOM) and dextran sodium sulfate (DSS) were combined to chemically build a CAC mouse model for 14 weeks. Each drug group was given intragastrically from the 5th week to the 14th week, once per day. An equal volume of water was fed to the normal and model groups. The mouse survival rate, colon length, weight, and pathological alterations were assessed. The protein expressions of Wnt-3a protein signaling (Wnt3a), β-catenin, Non-phosphor-β-catenin (Non-p-β-catenin), and cholesterol-binding glycoproteins 133 (CD133) were detected by Western blot. The localization and expression of the cluster of differentiation (CD) 80 and CD11 antigen-like family member B (CD11b) were detected by immunohistochemistry (IHC). The colon organoids derived from CAC mice were isolated and cultured to detect the expression of Wnt signaling pathway-related proteins. ResultThe survival rate of the CAC mice was improved by QHJ treatment and the number of colon tumors was inhibited significantly. Compared with those in the normal group, the expression levels of Wnt3a, β-catenin, Non-p-β-catenin, and CD133 in colon tissues in the model group were significantly increased (P<0.05, P<0.01). Compared with those in the model group, the levels of Wnt3a and β-catenin in the QHJ-L group were significantly decreased (P<0.01), and the protein levels of Wnt3a, β-catenin, Non-p-β-catenin, and CD133 in the QHJ-H group were significantly decreased (P<0.05, P<0.01). Meanwhile, the expression level of CD11b in the model group was significantly increased compared with that in the normal group while the CD80 level was significantly decreased (P<0.05, P<0.01). Compared with those in the model group, CD11b in QHJ-L and QHJ-H groups was significantly decreased, and CD80 was significantly increased(P<0.05, P<0.01). The expressions of Non-p-β-catenin and CD133 in colonic organoids of CAC model mice were significantly increased, while QHJ treatment could inhibit the expressions of Non-p-β-catenin and CD133 in colonic organoids (P<0.01). ConclusionQHJ could inhibit the inflammation-cancer development in CAC mice, the mechanism of which might be related to regulating the microenvironment and inhibiting the over-activation of Wnt signaling.
3.Study on TCM Medication Law in Acute Gouty Arthritis Based on Data Mining
Qin WU ; Yanan ZHANG ; Yixuan LIU ; Yuzhe CAI ; Jing CHEN ; Jingjing YANG ; Zheng LUO ; Yihui DENG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(7):25-31
Objective To explore the characteristics of TCM prescriptions for acute gouty arthritis based on data mining methods;To provide reference for clinical treatment.Methods The clinical literature on the TCM treatment of acute gouty arthritis was retrieved from CNKI,Wanfang Data,VIP and SinoMed.The obtained formulas were input into Excel 2019 to establish a database,and SPSS Modeler 18.0,SPSS Statistics 26.0 and Cytoscape 3.9.1 were used for frequency analysis,association rule analysis,clustering analysis and factor analysis.Results A total of 290 articles meeting the requirements were included,including 295 prescriptions,involving 218 kinds of Chinese materia medica,with a total frequency of 3 573 times.24 kinds of Chinese materia medica,including Coicis Semen,Phellodendri Chinensis Cortex,Atractylodis Rhizoma,Smilacis Glabrae Rhizoma,Dioscoreae Spongiosae Rhizoma,Glycyrrhizae Radix et Rhizoma,Achyranthis Bidentatae Radix were used frequently in the treatment of acute gouty arthritis.The commonly used drugs were heat-clearing drugs,moisture-clearing drugs,blood circulation-activating drugs for removing blood stasis,and wind-dampness drugs.The property was mainly cold,the taste was mainly bitter,and the meridians were mainly liver,stomach,spleen and kidney meridians.The analysis of high-frequency drug association rules obtained 22 drug combinations,among which the core drug pairs were Phellodendri Chinensis Cortex-Atractylodis Rhizoma,Coicis Semen-Atractylodis Rhizoma-Phellodendri Chinensis Cortex.Clustering analysis obtained 4 clustering methods,and factor analysis obtained 9 common factors.Conclusion The main treatment of acute gouty arthritis by TCM is clearing heat and dampness,removing blood stasis and clearing collaterals,tonifying liver and kidney,regulating spleen and stomach,which could provide reference for the clinical treatment of acute gouty arthritis.
4.Prognostic significance of textbook outcome in advanced gastric patients who underwent neoadjuvant chemotherapy followed by surgical resection
Yihui TANG ; Zening HUANG ; Qiyue CHEN ; Ping LI ; Jianwei XIE ; Jiabin WANG ; Jianxian LIN ; Jun LU ; Longlong CAO ; Mi LIN ; Ruhong TU ; Chaohui ZHENG ; Changming HUANG
Chinese Journal of Surgery 2024;62(5):379-386
Objective:To investigate the risk factors and prognostic value of the textbook outcome (TO) in patients with advanced gastric cancer (AGC) who underwent neoadjuvant chemotherapy followed by surgical resection.Methods:This is a retrospective cohort study. A total of 253 patients with AGC who underwent neoadjuvant chemotherapy combined with gastrectomy and D2 lymphadenectomy in the Department of Gastric Surgery, Fujian Medical University Union Hospital from January 2010 to December 2019 were retrospectively included. There were 195 males and 58 females, aged (60.3±10.0) years (range: 27 to 75 years). The patients were then divided into the TO group ( n=168) and the non-TO group ( n=85). Multivariate Logistic regression was used to analyze the independent predictors of TO. Univariate and multivariate Cox analysis were used to analyze independent prognosis factors for overall survival (OS) and disease-free survival (DFS). Propensity score matching was performed to balance the TO and non-TO groups, and the Kaplan-Meier method was used to calculate survival rates and draw survival curves. Results:Among the 253 patients, 168 patients (66.4%) achieved TO. The Eastern Cooperative Oncology Group score ( OR=0.488, 95% CI: 0.278 to 0.856, P=0.012) and ypN stage ( OR=0.626, 95% CI:0.488 to 0.805, P<0.01) were independently predictive of TO. Multivariate analysis revealed that TO was an independent risk factor for both OS ( HR=0.662, 95% CI: 0.457 to 0.959, P=0.029) and DFS ( HR=0.687, 95% CI: 0.483 to 0.976, P=0.036). After matching, the 5-year OS rate (42.2% vs. 27.8%) and the 5-year DFS rate (37.5% vs. 27.8%) were significantly higher in the TO group than in the non-TO group (both P<0.05). Furthermore, patients in the non-TO group benefited significantly from postoperative chemotherapy (both P<0.05), but those in the TO group did not (both P>0.05). Conclusion:TO is an independent prognosis factor in patients undergoing neoadjuvant chemotherapy and surgery for AGC and is associated with postoperative chemotherapy benefits.
5.Prognostic significance of textbook outcome in advanced gastric patients who underwent neoadjuvant chemotherapy followed by surgical resection
Yihui TANG ; Zening HUANG ; Qiyue CHEN ; Ping LI ; Jianwei XIE ; Jiabin WANG ; Jianxian LIN ; Jun LU ; Longlong CAO ; Mi LIN ; Ruhong TU ; Chaohui ZHENG ; Changming HUANG
Chinese Journal of Surgery 2024;62(5):379-386
Objective:To investigate the risk factors and prognostic value of the textbook outcome (TO) in patients with advanced gastric cancer (AGC) who underwent neoadjuvant chemotherapy followed by surgical resection.Methods:This is a retrospective cohort study. A total of 253 patients with AGC who underwent neoadjuvant chemotherapy combined with gastrectomy and D2 lymphadenectomy in the Department of Gastric Surgery, Fujian Medical University Union Hospital from January 2010 to December 2019 were retrospectively included. There were 195 males and 58 females, aged (60.3±10.0) years (range: 27 to 75 years). The patients were then divided into the TO group ( n=168) and the non-TO group ( n=85). Multivariate Logistic regression was used to analyze the independent predictors of TO. Univariate and multivariate Cox analysis were used to analyze independent prognosis factors for overall survival (OS) and disease-free survival (DFS). Propensity score matching was performed to balance the TO and non-TO groups, and the Kaplan-Meier method was used to calculate survival rates and draw survival curves. Results:Among the 253 patients, 168 patients (66.4%) achieved TO. The Eastern Cooperative Oncology Group score ( OR=0.488, 95% CI: 0.278 to 0.856, P=0.012) and ypN stage ( OR=0.626, 95% CI:0.488 to 0.805, P<0.01) were independently predictive of TO. Multivariate analysis revealed that TO was an independent risk factor for both OS ( HR=0.662, 95% CI: 0.457 to 0.959, P=0.029) and DFS ( HR=0.687, 95% CI: 0.483 to 0.976, P=0.036). After matching, the 5-year OS rate (42.2% vs. 27.8%) and the 5-year DFS rate (37.5% vs. 27.8%) were significantly higher in the TO group than in the non-TO group (both P<0.05). Furthermore, patients in the non-TO group benefited significantly from postoperative chemotherapy (both P<0.05), but those in the TO group did not (both P>0.05). Conclusion:TO is an independent prognosis factor in patients undergoing neoadjuvant chemotherapy and surgery for AGC and is associated with postoperative chemotherapy benefits.
6.Epidemiological investigation of a school COVID-19 outbreak in Shanghai
Zhongwang WANG ; Yan XIE ; Yu ZHANG ; Lingna KONG ; Yihui ZHENG ; Yuyan ZHANG
Shanghai Journal of Preventive Medicine 2023;35(11):1068-1073
ObjectiveTo describe a COVID-19 outbreak due to SARS-CoV-2 Omicron variant in a school and provide suggestions for COVID-19 prevention and control. MethodsData on the COVID-19 outbreak in a school in Putuo District of Shanghai were collected from November 14 to December 20, 2022. Epidemiological characteristics, incidence rate of secondary cases and response measures were described and analyzed. ResultsA total of 27 COVID-19 cases were identified infected with SARS-CoV-2 Omicron BA.5.2 variant, including 14 students (51.9%) and 13 family members / teachers living with those students (48.1%). The first case occurred on November 14, with peak incidence during November 16-18. The median generation interval of the second generation cases was 2 (2,3) days. The index case (case 1, a student) had a clear contact history outside the school, which was found through routine examination in key populations in the school. Immediate management was conducted after the notification. All the second generation cases were exposed students in the same class with case 1, which were identified during the quarantine, whereas the third generation cases were their family members/teachers living with the second generation cases. The incidence rate within the class and school were 36.8% and 3.0%, respectively. No further social transmission was found outside the school. ConclusionEarly detection, multi-sectoral collaboration, prompt control and quarantine measures are effective in containing SARS-CoV-2 transmission. Health promotion, surveillance, ventilation and prophylactic disinfection should be reinforced in schools, office buildings and other gathering places.
7.Effect of Zuogui Jiangtang Tongmai Prescription on SCFAs/GPR43/GLP-1/GLP-1R Signaling Pathway in Rats with Diabetes Mellitus Complicated with Cerebral Infarction
Xun LIU ; Hua LIU ; Lanyu PENG ; Zheng LUO ; Yihui DENG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(21):86-93
ObjectiveTo explore the potential mechanism of Zuogui Jiangtang Tongmai prescription (ZJT) in the treatment of diabetes mellitus complicated with cerebral infarction (DM-CI) in rats based on the short-chain fatty acids (SCFAs)/G protein-coupled receptor 43 (GPR43)/glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1R) signaling pathway. MethodSixty SD rats were randomly divided into sham operation group, model group, low- and high-dose ZJT groups (12, 24 g·kg-1), western medicine group (140 mg·kg-1 pioglitazone metformin tablets + 27 mg·kg-1 enteric-coated aspirin tablets). Except for the sham operation group, all other groups were fed a high-sugar high-fat diet for 4 weeks and then subjected to intraperitoneal injection of 1% streptozotocin at 35 mg·kg-1 combined with middle cerebral artery occlusion (MCAO) to establish a DM-CI rat model. The corresponding interventions were performed with distilled water, low-dose ZJT, high-dose ZJT, pioglitazone metformin tablets, and enteric-coated aspirin tablets. After surgery, National Institutes of Health Stroke Scale (NIHSS) scoring and triphenyltetrazolium chloride (TTC) staining to measure the rat's cerebral infarct volume were carried out. Random blood glucose levels were measured, and hematoxylin-eosin (HE) staining was used to observe histopathological changes in rat brain tissues. Gas chromatography was employed to detect the content of SCFAs in the cecum contents. Enzyme-linked immunosorbent assay (ELISA) was adopted to measure serum GLP-1 level. Western blot was used to detect the protein expression of GPR43 in rat ileal tissues and GLP-1R in the ischemic brain tissues. ResultCompared with the sham operation group, the model group showed significantly increased NIHSS scores, random blood glucose levels, and cerebral infarct volumes (P<0.01), and significantly decreased SCFAs content, GLP-1 levels, and GPR43 and GLP-1R protein expression (P<0.01). Compared with the model group, the high-dose ZJT group and the western medicine group exhibited significantly reduced NIHSS scores, random blood glucose levels, and cerebral infarct volumes (P<0.05, P<0.01), and significantly increased SCFAs content, GLP-1 levels, and GPR43 and GLP-1R protein expression (P<0.01). ConclusionZJT can improve glucose metabolism disorder and reduce neurological damage in DM-CI rats, and its mechanism may be related to the increase in SCFAs content and the upregulation of the GPR43/GLP-1/GLP-1R signaling pathway.
8.Mechanism of Xumingtang in Gu Jin Lu Yan for Treatment of Ischemic Stroke Based on HIF-1α/NLRP3 Pathway-mediated Pyroptosis
Yuzhe CAI ; Dingxiang LI ; Zheng LUO ; Yixuan LIU ; Jingjing YANG ; Qin WU ; Yanan ZHANG ; Jing CHEN ; Yihui DENG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(17):9-17
ObjectiveTo investigate the mechanism of Xumingtang in Gu Jin Lu Yan (《古今录验》) in regulating cell pyroptosis through the hypoxia-inducible factor-1α (HIF-1α)/NOD-like receptor pyrin domain-containing protein 3 (NLRP3) pathway in ischemic stroke (IS). MethodSD rats were randomly divided into a sham operation group, a model group, low- and high-dose Xumingtang groups, and a metformin group, with 20 rats in each group. Oral administration was performed for 3 days, and tissue samples were collected. Differential messenger RNA (mRNA) was screened using high-throughput sequencing, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on key differentially expressed genes. The modified neurological severity score (mNSS) and 2,3,5-triphenyltetrazolium chloride (TTC) staining were used to evaluate the effect of brain infarction. Hematoxylin-eosin (HE) staining was used for pathological morphological observation of brain tissue. Enzyme-linked immunosorbent assay (ELISA) was used to compare the levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) in the ischemic cortical region. Double staining immunohistochemistry was used to detect the co-localization of HIF-1α and NLRP3. Real-time quantitative polymerase chain reaction (PCR) was performed to detect the mRNA expression of NLRP3, HIF-1α, Caspase-1 (CASP-1), and gasdermin D (GSDMD). Western blot was used to detect the protein expression of HIF-1α, NLRP3, CASP-1, and GSDMD. ResultA total of 5 705 differentially expressed genes (2 733 downregulated and 2 972 upregulated) were obtained by mRNA sequencing. After conversion to homologous genes and intersection with the pyroptosis gene set, 95 key differentially expressed pyroptosis genes were obtained. Compared with the sham operation group, the model group showed significantly increased mNSS scores, larger brain infarction areas (P<0.01), diverse neuronal morphology, disordered arrangement, widened cell gaps, significantly increased levels of IL-1β and IL-18 in the ischemic cortical region (P<0.01), enhanced co-localization fluorescence intensity, and significantly increased mRNA and protein expression levels of HIF-1α, NLRP3, CASP-1, and GSDMD (P<0.01). Compared with the model group, the high-dose Xumingtang group showed the most significant improvement in neurological function scores and brain infarction areas (P<0.01). The neuronal integrity and arrangement were more complete, and the cell gaps were narrower in all groups with drug treatment, with significantly reduced co-localization fluorescence intensity. Xumingtang could reduce the levels of IL-1β, IL-18, and the mRNA and protein expression of HIF-1α, NLRP3, CASP-1, and GSDMD (P<0.05, P<0.01), with the high-dose Xumingtang group showing the most significant effect (P<0.01). ConclusionXumingtang in Gu Jin Lu Yan can inhibit cell pyroptosis and promote neurological function recovery after IS, which may be related to the inhibition of the HIF-1α/NLRP3 pathway.
9.Experimental study on the improvement of inflammatory response in rats with cerebral ischemia by Chinese ultrasound drug permeation electrotherapy device
Jingjing YANG ; Zheng LUO ; Yuzhe CAI ; Yixuan LIU ; Dingxiang LI ; Yihui DENG
International Journal of Traditional Chinese Medicine 2023;45(1):54-59
Objective:To observe the effects of Traditional Chinese Medicine (TCM)ultrasound drug permeation electrotherapy device on the inflammatory response of rats with cerebral ischemia, and to provide an experimental basis for the clinical application of TCM ultrasound drug permeation electrotherapy device in the treatment of cerebral ischemia.Methods:A total of 72 SD rats were randomly divided into sham-operation group (12 rats) and modeling group (60 rats). The middle cerebral artery occlusion (MCAO) model was prepared by thread embolism in the model group. The rats were divided into model group, Chinese medicine tablet group, blank tablet + TCM ultrasound drug permeation electrotherapy group (hereinafter referred to as "blank tablet + electrotherapy group"), Chinese medicine tablet + TCM ultrasound drug permeation electrotherapy group (hereinafter referred to as "Chinese medicine tablet + electrotherapy group") and butylphthalide group according to the random number table method, with 12 rats in each group. The corresponding treatment was given continuously for 7 days. The neurological function was scored using Longa method evaluation criteria; TTC staining was used to observe the infarct volume and calculate the percentage of infarct volume; HE staining was used to observe the cell morphology of cortical area in each group of rats; ELISA was used to detect the serum TNF-α and IL-1β levels in each group of rats; TLR4, MyD88 and NF-κBp65 protein expressions in hippocampal tissue of each group of rats on the infarct side were detected by Western blot method.Results:Compared with the model group, the neurological function scores of rats in the blank tablet + electrotherapy group, the herbal tablet + electrotherapy group, and the butylphthalein group significantly decreased ( P<0.05), the percentage of cerebral infarct volume significantly decreased ( P<0.05), the contents of serum TNF-α and IL-1β significantly decreased ( P<0.05), and the expressions of TLR4 (0.42±0.07, 0.31±0.07, 0.19±0.04 vs. 0.68±0.14), MyD88 (0.39±0.12, 0.30±0.07, 0.23±0.11 vs. 0.67±0.10), NF-κBp65 (0.32±0.03, 0.27±0.02, 0.17±0.03 vs. 0.57±0.12) protein in hippocampal tissue significantly decreased ( P<0.05). Conclusion:The TCM ultrasound drug permeation electrotherapy device can inhibit TLR4, MyD88, NF-κBp65 protein expressions and reduce the release of serum inflammatory factors TNF-α and IL-1β, thus exerting cerebral ischemic protective effects.
10.Relationship Between NLRP3 Inflammasome and Ischemic Stroke and Intervention Effect of Traditional Chinese Medicine
Xun LIU ; Yujia LI ; Zheng LUO ; Yue ZHOU ; Yihui DENG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(18):225-236
Ischemic stroke, also known as cerebral infarction, is the most common type of stroke. Ischemic stroke is extremely harmful with high rates of morbidity, incidence, disability, and mortality, bringing a huge burden on society and families. As a result, finding new and effective prevention and treatment methods is critical. The pathological mechanism of ischemic stroke is very complex and superimposed, with inflammatory response serving as a critical pathological link in the ischemic stroke cascade injury process. NOD-like receptor 3 (NLRP3) is an intracellular sensor, and the inflammatory cascade mediated by the activated NLRP3 inflammasome can exacerbate ischemic stroke injury through the release of inflammatory factors. Taking the NLRP3 inflammasome as the entry point, a large number of experimental studies on the intervention of traditional Chinese medicine (TCM) in the assembly and activation of NLRP3 inflammasome have been carried out, which proved that Chinese medicinal monomers or prescriptions with the main functions of tonifying deficiency, clearing heat and removing toxin, eliminating phlegm, promoting circulation and resolving stasis can interfere with the assembly and activation of NLRP3 inflammasome, reduce the inflammatory response, and relieve ischemic stroke. This study reviewed the assembly and activation of NLRP3 inflammasome, the mechanism of NLRP3 inflammasome in ischemic stroke, and the prevention and treatment of ischemic stroke by TCM through regulation of the NLRP3 inflammasome, which provides a new entry point for the pathological mechanism of ischemic stroke and a direction for the development of new treatments for ischemic stroke.

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